This Article Full Text Full Text (PDF) All Versions of this Article: 145/10/4615    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, H. Articles by Wong, A. O. L. Search for Related Content PubMed PubMed Citation Articles by Zhou, H. Articles by Wong, A. O. L.

Novel Aspects of Growth Hormone (GH) Autoregulation: GH-Induced GH Gene Expression in Grass Carp Pituitary Cells through Autocrine/Paracrine Mechanisms

Department of Zoology (H.Z., W.K.W.K., A.O.L.W.), University of Hong Kong, Hong Kong; Department of Biochemistry (W.K.K.H.), Chinese University of Hong Kong, Hong Kong; and Endocrinology and Reproduction Research Branch (S.S.S.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510

Address all correspondence and requests for reprints to: Dr. Anderson O. L. Wong, Associate Professor, Room 4S-12, Kadoorie Biological Sciences Building, Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong SAR, People’s Republic of China. E-mail: olwong{at}hkucc.hku.hk.

GH feedback on its own secretion at the pituitary level has been previously reported, but the mechanisms involved have not been elucidated. Here we examined the autocrine/paracrine effects of GH on GH synthesis using grass carp pituitary cells as a cell model. GH receptors were identified in carp somatotrophs, and their activation by exogenous GH increased steady-state GH mRNA levels and GH production. Removal of endogenous GH by immunoneutralization using GH antiserum inhibited basal as well as stimulated GH mRNA expression induced by GH-releasing factors in fish, including GnRH, apomorphine, and pituitary adenylate cyclase-activating polypeptide-38. Cytosolic mature GH mRNA levels were elevated by GH treatment and reduced by GH antiserum, whereas nuclear GH primary transcripts were almost undetectable after GH immunoneutralization. Inhibition of Janus kinase-2 (JAK₂), phosphoinositide 3-kinase, and MAPK also abolished GH-induced steady-state GH mRNA expression. GH immunoneutralization in pituitary cells pretreated with actinomycin D induced a marked decrease in the half-life of GH mRNA, indicating that the clearance of GH transcripts could be enhanced by removing endogenous GH. These results provide evidence that GH can serve as a novel intrapituitary autocrine/paracrine factor maintaining GH gene expression in somatotrophs, and this action is mediated by JAK₂/MAPK and JAK₂/phosphoinositide 3-kinase cascades coupled to GH receptors.

This article has been cited by other articles:

				K. H. Sze, H. Zhou, Y. Yang, M. He, Y. Jiang, and A. O. L. Wong Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Growth Hormone (GH)-Releasing Factor in Grass Carp: II. Solution Structure of a Brain-Specific PACAP by Nuclear Magnetic Resonance Spectroscopy and Functional Studies on GH Release and Gene Expression Endocrinology, October 1, 2007; 148(10): 5042 - 5059. [Abstract] [Full Text] [PDF]

				X. Wang, M. M. S. Chu, and A. O. L. Wong Signaling mechanisms for {alpha}2-adrenergic inhibition of PACAP-induced growth hormone secretion and gene expression grass carp pituitary cells Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1750 - E1762. [Abstract] [Full Text] [PDF]

				A. O. L. Wong, M. C. Y. Chuk, H. C. Chan, and E. K. Y. Lee Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E203 - E214. [Abstract] [Full Text] [PDF]

				A. O. L. Wong, W. Li, C. Y. Leung, L. Huo, and H. Zhou Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Growth Hormone (GH)-Releasing Factor in Grass Carp. I. Functional Coupling of Cyclic Adenosine 3',5'-Monophosphate and Ca2+/Calmodulin-Dependent Signaling Pathways in PACAP-Induced GH Secretion and GH Gene Expression in Grass Carp Pituitary Cells Endocrinology, December 1, 2005; 146(12): 5407 - 5424. [Abstract] [Full Text] [PDF]

				H. Zhou, Y. Jiang, W. K W Ko, W. Li, and A. O L Wong Paracrine regulation of growth hormone gene expression by gonadotrophin release in grass carp pituitary cells: functional implications, molecular mechanisms and signal transduction J. Mol. Endocrinol., April 1, 2005; 34(2): 415 - 432. [Abstract] [Full Text] [PDF]

				H. Zhou, X. Wang, W. K. W. Ko, and A. O. L. Wong Evidence for a Novel Intrapituitary Autocrine/Paracrine Feedback Loop Regulating Growth Hormone Synthesis and Secretion in Grass Carp Pituitary Cells by Functional Interactions between Gonadotrophs and Somatotrophs Endocrinology, December 1, 2004; 145(12): 5548 - 5559. [Abstract] [Full Text] [PDF]